Utilization of Human Induced Pluripotent Stem Cells for Cardiac Repair

Abstract

The paracrine effect, mediated by chemical signals that induce a physiological response on neighboring cells in the same tissue, is an important regenerative mechanism for stem cell-based therapy. Exosomes are cell-secreted nanovesicles (50-120 nm) of endosomal origin, and have been demonstrated to be a major contributor to the observed stem cell-mediated paracrine effect in the cardiac repair process. Following cardiac injury, exosomes deriving from exogenous stem cells have been shown to regulate cell apoptosis, proliferation, angiogenesis, and fibrosis in the infarcted heart. Exosomes also play a crucial role in the intercellular communication between donor and recipient cells. Human induced pluripotent stem cells (hiPSCs) are promising cell sources for autologous cell therapy in regenerative medicine. Here, we review recent advances in the field of progenitor-cell derived, exosome-based cardiac repair, with special emphasis on exosomes derived from hiPSCs.

Keywords: cardiac; exosomes; induced pluripotent stem cells; regeneration; repair.

FIGURE 1

Schematic representation of the cardiac delivery of exosomes from iPSCs and other stem cells. Exosomes were delivered to the ischemic heart tissue through intravenous, intracoronary or intramyocardial which may lead to cardio-protection through the effects of anti-apoptosis, angiogenesis, anti-fibrosis and cell cycle activation.

FIGURE 2

Schematic representation of the individualized cardiac therapy with exosomes generated from iPSCs and its derivatives. Patient-specific Cells (A) were isolated and reprogrammed into iPSCs (B), then differentiated into its derivatives including iPSC-CMs, iPSC-ECs and iPSC-SMCs (C). Exosomes (D) generated from iPSCs and its derivatives were then used as a platform for personalized cardiac therapy by simulating endogenous repair through intracoronary, intramyocardial or intravenous delivery (E).